This proposal seeks to carry out experiments that will relate long-term memory formation in the hippocampus with working memory in the prefrontal cortex (PFC) by simultaneously monitoring ensemble activity in these regions during spatial and non-spatial memory tasks. By relating this activity to neural patterns observed during REM and NREM sleep we seek to find evidence of mnemonic reactivation encompassing multiple brain regions. The first set of experiments will establish this structure by recording from ensembles of individual neurons in rodent PFC during acquisition and performance of working memory tasks. Working memory can be thought of as the active maintenance and use of selective long-term memory representations. Interactions between the hippocampus and prefrontal cortex may serve as the basis for this process. Anatomical and physiological evidence indicates that ventral hippocampus and PFC are directly interconnected and receive related dopaminergic innervation thus providing a substrate for these mnemonic interactions. Having identified potential neural representations of working memory in hippocampal and prefrontal regions through multiple neuronal recording we will examine the role of key cellular and molecular mechanisms in this process as well as determining the nature of processing of mnemonic information that occurs during different stages of sleep. This work is motivated by recent observations of reactivation of experience-related neural patterns in the hippocampus during both NREM and REM sleep that will be extended into the PFC. These studies will contribute to our understanding of the relationship between the hippocampus and prefrontal cortex during memory formation, the role of sleep in processing of mnemonic information, and the contribution of specific receptors in these functions. These results will provide insight in the nature of memory and memory disorders as well as disorders that have been related to prefrontal function such as schizophrenia.